EDECIO CUNHA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/60 - Laboratório de Imunologia Clínica e Alergia, Hospital das Clínicas, Faculdade de Medicina - Líder
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
conferenceObject Benznidazole treatment is associated with Trypanosoma cruzi blood PCR negativity and less cardiac lesions in Chagas disease: NIH SaMitrop Study(2017) CARDOSO, C. S.; SABINO, E. C.; OLIVEIRA, C. D. L.; OLIVEIRA, L. C.; FERREIRA, A. M.; BIERRENBACH, A. L.; SILVA, J. L. P.; COLOSIMO, E. A.; CUNHA-NETO, E.; RIBEIRO, A. L. P.conferenceObject Evaluation of the Profile of Circulating microRNAs in Individuals with Recent Type 1 Diabetes and Healthy Controls(2017) SANTOS, Aritania S.; FERREIRA, Ludmila R.; FUKUI, Rosa T.; CUNHA-NETO, Edecio; SILVA, Maria Elizabeth R.conferenceObject CIRCULATING MIRNAS PROFILE AS POTENTIAL SIGNATURE OF BENZNIDAZOLE TREATMENT TOXICITY IN CHAGAS PATIENTS(2017) CANDIDO, Darlan da Silva; CUNHA-NETO, Edecio; RIGAUD, Vagner O.; OLIVEIRA, Lea C. de; MOREIRA, Carlos Henrique V.; JUNIOR, Nelson G.; SOUZA, Marcela de; SABINO, Ester C.; FERREIRA, Ludmila R.conferenceObject POTENTIATION OF BENZNIDAZOLE EFFECT BY COADMINISTRATION OF REPURPOSED DRUGS ACTING IN THE INVASION OF HOST CELLS BY TRYPANOSOMA CRUZI(2017) PANDEY, Ramendra P.; SAVOIA, Marilda; SABINO, Ester; KALIL, Jorge; CUNHA-NETO, Edecio- Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization(2017) MARTINS, Carlo de Oliveira; DEMARCHI, Lea; FERREIRA, Frederico Moraes; POMERANTZEFF, Pablo Maria Alberto; BRANDAO, Carlos; SAMPAIO, Roney Orismar; SPINA, Guilherme Sobreira; KALIL, Jorge; CUNHA-NETO, Edecio; GUILHERME, LuizaAutoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/ organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
- p16(INK4a) Expression and Immunologic Aging in Chronic HIV Infection (vol 11, e0166759, 2016)(2017) RIBEIRO, Susan Pereira; MILUSH, Jeffrey M.; CUNHA-NETO, Edecio; KAILAS, Esper G.; KALIL, Jorge; PASSERO, Luiz Felipe D.; HUNT, Peter W.; DEEKS, Steven G.; NIXON, Douglas F.; SENGUPTA, Devi
- An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling(2017) CUNHA-NETO, Edecio; ROSA, Daniela S.; HARRIS, Paul E.; OLSON, Tim; MORROW, Alex; CIOTLOS, Serban; HERST, Charles V.; RUBSAMEN, Reid MartinThe threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.
- Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients(2017) RIGAUD, Vagner Oliveira-Carvalho; FERREIRA, Ludmila R. P.; AYUB-FERREIRA, Silvia M.; AVILA, Monica S.; BRANDAO, Sara M. G.; CRUZ, Fatima D.; SANTOS, Marilia H. H.; CRUZ, Cecilia B. B. V.; ALVES, Marco S. L.; ISSA, Victor S.; GUIMARAES, Guilherme V.; CUNHA-NETO, Edecio; BOCCHI, Edimar A.Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from ""Carvedilol Effect on Chemotherapy-induced Cardiotoxicity"" (CECCY trial), which included 56 female patients (49.9 +/- 3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1,-133b,-146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6 +/- 0.3 to 46.7 +/- 5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3 +/- 0.5 to 63.8 +/- 0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2 +/- 1.0 to 58.8 +/- 2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p = 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.
- Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-gamma-Driven Inflammation(2017) MEDINA, Tiago Silva; OLIVEIRA, Gabriela Goncalves; SILVA, Maria Claudia; DAVID, Bruna Araujo; SILVA, Grace Kelly; FONSECA, Denise Morais; SESTI-COSTA, Renata; FRADE, Amanda Farage; BARON, Monique Andrade; IANNI, Barbara; PEREIRA, Alexandre Costa; CHEVILLARD, Christophe; CUNHA-NETO, Edecio; MARIN-NETO, Jose Antonio; SILVA, Joao SantanaThe identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-gamma-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-gamma blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-gamma, the bona fide culprit of Chagas disease cardiomyopathy.
- Chronic Chagas Heart Disease Management From Etiology to Cardiomyopathy Treatment(2017) BOCCHI, Edimar Alcides; BESTETTI, Reinaldo Bulgarelli; SCANAVACCA, Mauricio Ibrahim; NETO, Edecio Cunha; ISSA, Victor SarliTrypanosoma cruzi (T. cruzi) infection is endemic in Latin America and is becoming a worldwide health burden. It may lead to heterogeneous phenotypes. Early diagnosis of T. cruzi infection is crucial. Several biomarkers have been reported in Chagas heart disease (ChHD), but most are nonspecific for T. cruzi infection. Prognosis of ChHD patients is worse compared with other etiologies, with sudden cardiac death as an important mode of death. Most ChHD patients display diffuse myocarditis with fibrosis and hypertrophy. The remodeling process seems to be associated with etiopathogenic mechanisms and neurohormonal activation. Pharmacological treatment and antiarrhythmic therapy for ChHD is mostly based on results for other etiologies. Heart transplantation is an established, valuable therapeutic option in refractory ChHD. Implantable cardioverter-defibrillators are indicated for prevention of secondary sudden cardiac death. Specific etiological treatments should be revisited and reserved for select patients. Understanding and management of ChHD need improvement, including development of randomized trials. (C) 2017 by the American College of Cardiology Foundation.